PROJECT SUMMARY/ABSTRACT Women and men are at different risks for disorders that occur at different stages of the lifespan from development through aging and have critical implications for therapeutic efficacy. However, many of the mechanisms that explain these sex differences or disorders specific to women are still unclear. The mission of our Harvard BIRCWH is to develop the next generation of scientist-clinicians as leaders in the field of women's health and sex differences who will contribute to understanding sex-dependent vulnerabilities to clinical disorders and those specific to women. This competing renewal application seeks to continue to support an integrated interdisciplinary training program that is based on a translational approach to understanding differential incidences of disorders important for the health of women and how it differs from men. The program is modeled in the context of a lifespan perspective to identify etiologic mechanisms during fetal development, puberty, adulthood, and aging, including the child-bearing years and menopause. Further, an underlying assumption of our BIRCWH program is that an understanding of the role of hormones and genes will provide the basis for understanding sex-dependent vulnerabilities to clinical disorders. The Division of Women's Health at Brigham and Women's Hospital (BWH) and the Women, Heart and Brain Global Initiative at Massachusetts General Hospital (MGH) Research Institute, are the home sites for this endeavor, in the broader context of a Harvard-wide training program. The program capitalizes on the long tradition of interdisciplinary research in women's health and sex differences with mentors across Harvard institutions: BWH, MGH, Beth Israel- Deaconess Medical Center, Boston Children's Hospital, Dana Farber Cancer Institute, McLean Hospital, Harvard T.H. Chan School of Public Health, Harvard Medical School and the Eli & Edythe Broad Institute. Each BIRCWH scholar is assigned a team of mentors to operationalize translational thinking. Primary Mentors are in clinical or basic research and provide the site at which the scholar works. Secondary Mentors are in basic or clinical research (as a counterpart to the Primary) and help to guide thinking, coursework and readings, depending on the scholar's interests. Career Mentors advise scholars in the relevant departmental and academic structures for career advancement. Mentors in Health Disparities expose scholars to thinking about how the roles of hormones and genes in affected morbidity are influenced by socioenvironmental factors. The Harvard BIRCWH program focuses on disorders with higher incidence and/or differential expression in women than men including: Cardiovascular Disorders; Reproductive Endocrine & Neuroendocrine Disorders; Neuropsychiatric Disorders; Autoimmune Disorders; and Female Cancers. By capitalizing on the vast resources and faculty at Harvard and our 14-year successful BIRCWH history, Harvard is an ideal site for continuing to offer an integrated, interdisciplinary and truly translational program that will continue to train the next generation of leaders in women's health and sex differences in medicine.